Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases characterised by progressive bile duct injury, persistent cholestasis, fibrosis and eventual cirrhosis. Growing evidence indicates that epigenetic mechanisms, particularly microRNAs, play an important role in their pathogenesis. Among them, microRNA-155 (miR-155) has emerged as a central immunoregulatory molecule involved in both innate and adaptive immune responses. MicroRNA-155 regulates key inflammatory signalling pathways, including NF-κB and Janus kinase (JAK)/STAT, and interferes with bile acid homeostasis through suppression of the farnesoid X receptor, thereby contributing to sustained cholestasis and inflammatory injury. Increased expression of miR-155 has been observed in liver tissue, serum and peripheral blood mononuclear cells of patients with PBC and PSC, reflecting local and systemic immune activation. Importantly, miR-155 also links chronic inflammation with impairment of the mismatch repair system and microsatellite instability, promoting colorectal carcinogenesis in patients with PSC associated with ulcerative colitis. This review summarises the biogenesis, regulation and pathogenic significance of miR-155 in PBC and PSC, with particular emphasis on its role in mismatch repair dysfunction and emerging therapeutic implications.